{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:11:18Z","timestamp":1788459078913,"version":"build-2803163510"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:sec id=\"ab-cbr220019-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Determining whether neurofilament light chain (NfL) elevations in patients who develop immune effector cell\u2013associated neurotoxicity syndrome (ICANS) occur before or after infusion of cellular product is important to identify high-risk patients and inform whether neuroaxonal injury is latent or a consequence of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr220019-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify serial NfL levels in patients undergoing cellular therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr220019-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This retrospective 2-center study examined plasma NfL levels in 30 patients with detailed medical and treatment history, including all major pretreatment and posttreatment risk factors. Exclusion criteria included dementia and severe, symptomatic central nervous system (CNS) involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr220019-7\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Patients\u2019 NfL levels were measured at 7 time points: baseline (prelymphodepletion), during lymphodepletion, postinfusion day (D) 1, D3, D7, D14, and D30. Prediction accuracy for the development of ICANS was next modeled using receiver operating characteristic (ROC) classification. Finally, univariate and multivariate modeling examined the association between NfL levels, ICANS, and potential risk factors including demographic (age, sex), oncologic (tumor burden, history of CNS involvement), neurologic (history of nononcologic CNS disease or neuropathy), and neurotoxic exposure histories (vincristine, cytarabine, methotrexate, or CNS radiotherapy).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr220019-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 30 patients (median [range] age, 64 [22-80] years; 12 women [40%] and 18 men [60%]) were included. Individuals who developed ICANS had elevations in NfL prior to lymphodepletion and chimeric antigen receptor T-cell infusion compared with those who did not develop ICANS (no ICANS: 29.4 pg\/mL, vs any ICANS: 87.6 pg\/mL;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Baseline NfL levels further predicted ICANS development with high accuracy (area under the ROC curve, 0.96), sensitivity (0.91), and specificity (0.95). Levels of NfL remained elevated across all time points, up to 30 days postinfusion. Baseline NfL levels correlated with ICANS severity but not demographic factors, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr220019-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In a subset of patients in this cross-sectional study, the risk of developing ICANS was associated with preexisting neuroaxonal injury that was quantifiable with plasma NfL level. This latent neuroaxonal injury was present prior to drug administration but was not associated with historic neurotoxic therapies or nononcologic neurologic disease. Preinfusion NfL may further permit early screening and identification of patients most at risk for ICANS. Additional studies are needed to determine NfL\u2019s utility as a predictive biomarker for early (preemptive or prophylactic) intervention and to delineate the origin of this underlying neural injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.3738","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T11:32:23Z","timestamp":1662031943000},"page":"1652","source":"Crossref","is-referenced-by-count":30,"title":["Assessment of Pretreatment and Posttreatment Evolution of Neurofilament Light Chain Levels in Patients Who Develop Immune Effector Cell\u2013Associated Neurotoxicity Syndrome"],"prefix":"10.1001","volume":"8","author":[{"given":"Omar H.","family":"Butt","sequence":"first","affiliation":[{"name":"Siteman Cancer Center, Department of Medicine, Division of Oncology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Y.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Department of Medicine, Division of Oncology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo F.","family":"Caimi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick H.","family":"Luckett","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie K.","family":"Wisch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Robert","family":"Derenoncourt","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory F.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos J. G.","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ohio State University Cancer Treatment and Research Center, The Ohio State University, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian L.","family":"Campian","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Department of Medicine, Division of Oncology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"DiPersio","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Department of Medicine, Division of Oncology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Ghobadi","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Department of Medicine, Division of Oncology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M.","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"5","key":"cbr220019r1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia.","volume":"378","author":"Park","year":"2018","journal-title":"N Engl J Med"},{"issue":"26","key":"cbr220019r2","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma.","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"issue":"12","key":"cbr220019r3","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1007\/s40263-018-0582-9","article-title":"Neurotoxicity associated with CD19-targeted CAR-T cell therapies.","volume":"32","author":"Gust","year":"2018","journal-title":"CNS Drugs"},{"issue":"4","key":"cbr220019r4","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells.","volume":"25","author":"Lee","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"issue":"10","key":"cbr220019r5","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders.","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"cbr220019r6","doi-asserted-by":"publisher","first-page":"ii127","DOI":"10.1093\/neuonc\/noaa215.535","article-title":"NCMP-24. 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ClinicalTrials.gov identifier: NCT03434769. Updated March 14, 2022. Accessed August 3, 2022. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03434769"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2795985\/jamaoncology_butt_2022_br_220019_1668658041.71398.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T11:05:37Z","timestamp":1668683137000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2795985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":15,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2022.3738","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}